Abstract
In 2006, the secondary metabolite leiodolide A was isolated from a newly discovered deep-sea sponge of the genus Leiodermatium. The 19-membered macrolide represented a new class of mixed polyketide, nonribosomal, peptide synthetase natural products. A total synthesis of leiodolide A is yet to be achieved and is of specific interest, not only for its complex structure and undefined stereochemistry, but also the potent cytotoxic properties it possesses, particularly towards leukaemia, non-small cell lung and ovarian cancers.
A synthetic strategy for leiodolide A must be flexible to overcome the currently unresolved stereochemistry and a convergent route towards the synthesis of the molecule required three subunits. Following the earlier synthesis of the C21-C25 vinyl stannane fragment, this work describes the synthesis of the C1-C10 subunit in the both possible diastereomeric forms. The synthesis of the two required C13 epimers of the C11-C20 subunit is also detailed accompanied by an investigation into potential fragment coupling, in preparation for total synthesis.
Type
Thesis, PhD Doctor of Philosophy
Rights
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/